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Photothermal conversion of light into heat energy is an intrinsic optical property of metal nanoparticles when irradiated using near-infrared radiation. However, the impact of size and shape on the photothermal behaviour of gold nanomakura particles possessing optical absorption within 600–700 nm as well as on incorporation in hydrogels is not well reported. In this study, nanomakura-shaped anisotropic gold nanoparticles (AuNMs) were synthesized via a surfactant-assisted seed-mediated protocol. Quaternary cationic surfactants having variable carbon tail length (n = 16, 14, 12) were used as capping for tuning the plasmon peak of gold nanomakura within a 600–700 nm wavelength. The aspect ratio as well as anisotropy of synthesized gold nanomakura can influence photothermal response upon near-infrared irradiation. The role of carbon tail length was evident via absorption peaks obtained from longitudinal surface plasmon resonance analysis at 670, 650, and 630 nm in CTAB-AuNM, MTAB-AuNM, and DTAB-AuNM, respectively. Furthermore, the impact of morphology and surrounding milieu of the synthesized nanomakuras on photothermal conversion is investigated owing to their retention of plasmonic stability. Interestingly, we found that photothermal conversion was exclusively assigned to morphological features (i.e., nanoparticles of higher aspect ratio showed higher temperature change and vice versa irrespective of the surfactant used). To enable biofunctionality and stability, we used kappa-carrageenan- (k-CG) based hydrogels for incorporating the nanomakuras and further assessed their photothermal response. Nanomakura particles in association with k-CG were also able to show photothermal conversion, depicting their ability to interact with light without hindrance. The CTAB-AuNM, MTAB-AuNM, and DTAB-AuNM after incorporation into hydrogel beads attained up to ≈17.2, ≈17.2, and ≈15.7 °C, respectively. On the other hand, gold nanorods after incorporation into k-CG did not yield much photothermal response as compared to that of AuNMs. The results showed a promising platform to utilize nanomakura particles along with kappa-carrageenan hydrogels for enabling usage on nanophotonic, photothermal, and bio-imaging applications.

BackgroundThermogenic beige adipocytes, which dissipate energy as heat, are found in neonates and adults. Recent studies show that neonatal beige adipocytes are highly plastic and contribute to >50% of beige adipocytes in adults. Neonatal beige adipocytes are distinct from recruited beige adipocytes in that they develop independently of temperature and sympathetic innervation through poorly defined mechanisms.MethodsWe characterized the neonatal beige adipocytes in the inguinal white adipose tissue (iWAT) of C57BL6 postnatal day 3 and 20 mice (P3 and P20) by imaging, genome-wide RNA-seq analysis, ChIP-seq analysis, qRT-PCR validation, and biochemical assays.ResultsWe found an increase in acetylated histone 3 lysine 27 (H3K27ac) on the promoter and enhancer regions of beige-specific gene UCP1 in iWAT of P20 mice. Furthermore, H3K27ac ChIP-seq analysis in the iWAT of P3 and P20 mice revealed strong H3K27ac signals at beige adipocyte-associated genes in the iWAT of P20 mice. The integration of H3K27ac ChIP-seq and RNA-seq analysis in the iWAT of P20 mice reveal epigenetically active signatures of beige adipocytes, including oxidative phosphorylation and mitochondrial metabolism. We identify the enrichment of GA-binding protein alpha (GABPα) binding regions in the epigenetically active chromatin regions of the P20 iWAT, particularly on beige genes, and demonstrate that GABPα is required for beige adipocyte differentiation. Moreover, transcriptomic analysis and glucose oxidation assays revealed increased glycolytic activity in the neonatal iWAT from P20.ConclusionsOur findings demonstrate that epigenetic mechanisms regulate the development of peri-weaning beige adipocytes via GABPα. Further studies to better understand the upstream mechanisms that regulate epigenetic activation of GABPα and characterization of the metabolic identity of neonatal beige adipocytes will help us harness their therapeutic potential in metabolic diseases.

The current education system significantly emphasizes tests and evaluations as crucial factors in determining a student's future career path. It has been shown that nursing students have moderate to high levels of Test Anxiety (TA), which results in decreased academic performance, low self-esteem, and an inability to complete the program and pursue a career in nursing successfully. This study aimed to determine nursing students' level of TA and its relationship with demographic characteristics. Four hundred twenty-one nursing students at seven private universities and colleges in Selangor participated in this cross-sectional study. The level of TA was measured using the TA Inventory (TAI). A total of 62.5% of the respondents had mild TA, 25.4% had moderate TA and 2.1% had severe TA. There were significant relationships between TA level and household income (χ2 = 6.70, p = 0.035) and ethnic groups (F (3,417) = 5.20, p = 0.002) where Chinese and Indians are protective from TA compared to the Malays and other ethnic groups and high anxiety was significant in the Ringgit Malaysia (RM 3000) and below group. The study's findings indicate that a significant percentage of nursing students involved in the research had mild to moderate levels of test anxiety (TA) and there is a significant association between TA and demographic characteristics. The results indicate the importance of early identification of TA and the need for interventions to overcome TA to ensure they are emotionally, physically, and academically successful.

A significant paradigm shift has been observed in the past decade in the area of theranostics owing to the development of various isotropic and anisotropic metal nanostructures, simultaneous with improved imaging modalities. Platinum-based nanostructures are advancing in a plethora of clinical applications as theranostics tools owing to their unique behavior concerning their size, shape, and surface chemistry at the nanoscale regime. Platinum nanostructures are optically active and provide significant potential to the field of theranostics by simplifying diagnosis and therapeutics, thus providing key solutions through nano-enabled technologies. The review emphasizes the potential of platinum nanostructures that have immense potential in vitro and in vivo scenarios as nanocarriers. Still, their potential in terms of photothermal active agents has not been well explored or reported. Nanotheranostics has emerged as a platform where various noble metal nanoparticles are effectively efficient as photothermal agents in bringing precision to therapy and diagnostics. Platinum, as an antioxidant and a stable nanocarrier, will enable them to act as photosensitizers when conjugated to affinity molecules and plays a key role in efficient treatment and diagnosis. The review envisions bringing together the possibilities of the safe-by-design synthesis of platinum nanostructures and their potential role in both in vitro and in vivo applications. A roadmap describing the challenges, pitfalls, and possibilities of influencing platinum nanostructures to overcome the existing biological/targeting barriers is elaborated. This review provides a literature survey on platinum nanostructures in theranostics, providing novel strategies in bio-imaging, diagnostics, and nanomedicine.

Breast cancer is one of the most common cancers in Malaysia. Recently, a new nomenclature was introduced for breast cancers with human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 1+, or 2+ with negative in situ hybridization (ISH), i.e., HER2-low breast cancer. In current clinical practice, these breast cancers are reported as HER2-negative. Clinical trials have shown that HER2-low breast cancer benefits from targeted therapy with anti-HER2 antibody-drug conjugates. Unfortunately, various challenges and obstacles are faced by local pathologists in HER2 testing, which may jeopardize the standard of care for patients with HER2-low breast cancer. This consensus guideline aims to elucidate standard practices pertaining to HER2 testing and HER2-low interpretation in Malaysia. Topics discussed among a panel of local experts include tissue sampling and handling, assay and antibody selection, result interpretation and reporting, and quality assurance. Practice recommendations made in this consensus guideline reflect current international guidelines and, where appropriate, adapted to the Malaysian landscape.

Background & Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disorder, with no approved treatment. Our previous work demonstrated the efficacy of a pan-ErbB inhibitor, Canertinib, in reducing steatosis and fibrosis in a murine fast-food diet (FFD) model of MASLD. The current study explores the effects of hepatocyte-specific ErbB1 (ie, epidermal growth factor receptor [EGFR]) deletion in the FFD model. Methods: EGFRflox/flox mice, treated with AAV8-TBG-CRE to delete EGFR specifically in hepatocytes (EGFR-KO), were fed either a chow-diet or FFD for 2 or 5 months. Results: Hepatocyte-specific EGFR deletion reduced serum triglyceride levels but did not prevent steatosis. Surprisingly, hepatic fibrosis was increased in EGFR-KO mice in the long-term study, which correlated with activation of transforming growth factor-β/fibrosis signaling pathways. Further, nuclear levels of some of the major MASLD regulating transcription factors (SREBP1, PPARγ, PPARα, and HNF4α) were altered in FFD-fed EGFR-KO mice. Transcriptomic analysis revealed significant alteration of lipid metabolism pathways in EGFR-KO mice with changes in several relevant genes, including downregulation of fatty-acid synthase and induction of lipolysis gene, Pnpla2, without impacting overall steatosis. Interestingly, EGFR downstream signaling mediators, including AKT, remain activated in EGFR-KO mice, which correlated with increased activity pattern of other receptor tyrosine kinases, including ErbB3/MET, in transcriptomic analysis. Lastly, Canertinib treatment in EGFR-KO mice, which inhibits all ErbB receptors, successfully reduced steatosis, suggesting the compensatory roles of other ErbB receptors in supporting MASLD without EGFR. Conclusions: Hepatocyte-specific EGFR-KO did not impact steatosis, but enhanced fibrosis in the FFD model of MASLD. Gene networks associated with lipid metabolism were greatly altered in EGFR-KO, but phenotypic effects might be compensated by alternate signaling pathways.

Two-dimensional strain imaging has an established role in the detection of subtle or subclinical left ventricular (LV) dysfunction in cardiomyopathies. The application of strain imaging, particularly longitudinal strain (LS), is emerging as a simple yet powerful tool in the detection of the early decline of LV function in valvular heart diseases also, including aortic regurgitation (AR). The advantages of strain imaging include its simplicity of the concept and imaging technique, its rapidity, and less interpersonal variability. The detection of lower strain values may help the clinician to optimally time the surgical intervention among asymptomatic individuals with preserved ejection fraction (EF). Such a preemptive approach is expected to improve the surgical results and offer better outcomes in terms of longevity and reverse remodeling of LV. Numerous studies have confirmed that a global LS value of 19.5% is the ideal cutoff for the detection of early LV dysfunction in AR. It has been shown in studies that a decreased strain correlates with mortality in medically treated as well as in operated patients. Apart from being potentially helpful in the timing of surgery in asymptomatic individuals, the estimation of strain is also useful in the detection of the contractile reserve, which is translated into better postoperative outcomes. If this finding is supported by future studies, strain imaging may eventually replace stress echocardiography in evaluating asymptomatic patients with valve diseases. Even in patients with advanced disease and low EF, strain values are helpful in identifying the subset of individuals who show better response to surgery. A cutoff of 12% appears to be useful in the detection of responders in this high-risk group. The usefulness of radial and circumferential strain, apical and basal rotation, and layered strain remains to be established. The extension of strain measurements in assessing myocardial work appears to be an attractive option for assessing LV function without load dependency.

The existing diagnosis and treatment modalities have major limitations related to their precision and capability to understand several stages of disease development. A superior therapeutic system consists of a multifunctional approach in early diagnosis of the disease with a simultaneous progressive cure, using a precise medical approach towards complex treatment. These challenges can be addressed via nanotheranostics and explore suitable approaches to improve health care. Nanotechnology in combination with theranostics as an unconventional platform paved the way for developing novel strategies and modalities leading to diagnosis and therapy for complex disease conditions, ranging from acute to chronic levels. Among the metal nanoparticles, gold nanoparticles are being widely used for theranostics due to their inherent non-toxic nature and plasmonic properties. The unique optical and chemical properties of plasmonic metal nanoparticles along with theranostics have led to a promising era of plausible early detection of disease conditions, and they enable real-time monitoring with enhanced non-invasive or minimally invasive imaging of several ailments. This review aims to highlight the improvement and advancement brought to nanotheranostics by gold nanoparticles in the past decade. The clinical use of the metal nanoparticles in nanotheranostics is explained, along with the future perspectives on addressing the key applications related to diagnostics and therapeutics, respectively. The scope of gold nanoparticles and their realistic potential to design a sophisticated theranostic system is discussed in detail, along with their implications in clinical advancements which are the needs of the hour. The review concluded with the challenges, opportunities, and implications on translational potential of using gold nanoparticles in nanotheranostics.

Abstract Visible-light-driven photo-fenton-like catalytic activity and photoelectrochemical (PEC) performance of nitrogen-doped brownmillerite KBiFe2O5 (KBFO) are investigated. The effective optical bandgap of KBFO reduces from 1.67 to 1.60 eV post N-doping, enabling both enhancement of visible light absorption and photoactivity. The photo-fenton activity of KBFO and N-doped KBFO samples were analysed by degrading effluents like Methylene Blue (MB), Bisphenol-A (BPA) and antibiotics such as Norfloxacin (NOX) and Doxycycline (DOX). 20 mmol of Nitrogen-doped KBFO (20N-KBFO) exhibits enhanced catalytic activity while degrading MB. 20N-KBFO sample is further tested for degradation of Bisphenol-A and antibiotics in the presence of H2O2 and chelating agent L-cysteine. Under optimum conditions, MB, BPA, and NOX, and DOX are degraded by 99.5% (0.042 min-1), 83% (0.016 min-1), 72% (0.011 min-1) and 95% (0.026 min-1) of its initial concentration respectively. Photocurrent density of 20N-KBFO improves to 8.83 mA/cm2 from 4.31 mA/cm2 for pure KBFO. Photocatalytic and photoelectrochemical (PEC) properties of N-doped KBFO make it a promising candidate for energy and environmental applications.

Background & Aims: Compelling evidence shows that glucagon-like peptide-1 (GLP-1) has a profound effect in restoring normoglycemia in type 2 diabetic patients by increasing pancreatic insulin secretion. Although L-cells are the primary source of circulating GLP-1, the current therapies do not target L-cells to increase GLP-1 levels. Our study aimed to determine the molecular underpinnings of GLP-1 secretion as an impetus to identify new interventions to target endogenous L-cells. Methods: We used genetic mouse models of intestine-specific overexpression of hypoxia-inducible factor (HIF)-1α and HIF-2α (VhlΔIE), conditional overexpression of intestinal HIF-2α (Hif-2αLSL;Vilin-Cre/ERT2), and intestine-specific HIF-2α knockout mice (Hif-2αΔIE) to show that HIF signaling, especially HIF-2α, regulates GLP-1 secretion. Results: Our data show that intestinal HIF signaling improved glucose homeostasis in a GLP-1–dependent manner. Intestinal HIF potentiated GLP-1 secretion via the lipid sensor G-protein–coupled receptor (GPR)40 enriched in L-cells. We show that HIF-2α regulates GPR40 in L-cells and potentiates fatty acid–induced GLP-1 secretion via extracellular regulated kinase (ERK). Using a genetic model of intestine-specific overexpression of HIF-2α, we show that HIF-2α is sufficient to increase GLP-1 levels and attenuate diet-induced metabolic perturbations such as visceral adiposity, glucose intolerance, and hepatic steatosis. Lastly, we show that intestinal HIF-2α signaling acts as a priming mechanism crucial for postprandial lipid-mediated GLP-1 secretion. Thus, disruption of intestinal HIF-2α decreases GLP-1 secretion. Conclusions: In summary, we show that intestinal HIF signaling, particularly HIF-2α, regulates the lipid sensor GPR40, which is crucial for the lipid-mediated GLP-1 secretion, and suggest that HIF-2α is a potential target to induce endogenous GLP-1 secretion.

Abstract g-C3N4/Ca2Fe2O5 heterostructures were successfully prepared by incorporating g-C3N4 into Ca2Fe2O5 (CFO). As prepared g-C3N4/CFO heterostructures were initially utilized to photodegrade organic effluent Methylene blue (MB) for optimization of photodegradation performance. 50% g-C3N4 content in CFO composition showed an enhanced photodegradation efficiency (~ 96%) over g-C3N4 (48.15%) and CFO (81.9%) due to mitigation of recombination of photogenerated charge carriers by Type-II heterojunction. The optimized composition of heterostructure was further tested for degradation of Bisphenol-A (BPA) under direct sunlight, exhibiting enhanced photodegradation efficiency of about 63.1% over g-C3N4 (17%) and CFO (45.1%). The photoelectrochemical studies at various potentials with and without light illumination showed significant improvement in photocurrent response for g-C3N4/Ca2Fe2O5 heterostructures (~ 1.9 mA) over CFO (~ 67.4 μA). These studies revealed efficient solar energy harvesting ability of g-C3N4/Ca2Fe2O5 heterostructures to be utilized for organic effluent treatment.

Plasmonic metal nanoparticles are widely used for many applications due to their unique optical and chemical properties. Over the past decade, anisotropic metal nanoparticles have been explored for imaging, sensing, and diagnostic applications. The variations and flexibility of tuning the size and shape of the metal nanoparticles at the nanoscale made them promising candidates for biomedical applications such as therapeutics, diagnostics, and drug delivery. However, safety and risk assessment of the nanomaterials for clinical purposes are yet to be made owing to their cytotoxicity. The toxicity concern is primarily due to the conventional synthesis route that involves surfactants as a structure-directing agent and as a capping agent for nanoparticles. Wet chemical methods employ toxic auxiliary chemicals. However, the approach yields monodispersed nanoparticles, an essential criterion for their intended application and a limitation of the green synthesis of nanoparticles using plant extracts. Several biocompatible counterparts such as polymers, lipids, and chitosan-based nanoparticles have been successfully used in the synthesis of safe nanomaterials, but there were issues regarding reproducibility and yield. Enzymatic degradation was one of the factors responsible for limiting the efficacy. Hence, it is necessary to develop a safer and nontoxic route towards synthesizing biocompatible nanomaterials while retaining morphology, high yield, and monodispersity. In this regard, deep eutectic solvents (DESs) and carrageenan as capping agent for nanoparticles can ensure the safety. Carrageenan has the potential to act as antibacterial and antiviral agent, and adds enhanced stability to the nanoparticles. This leads to a multidimensional approach for utilizing safe nanomaterials for advanced biomedical and clinical applications.

Background: First-time mothers may experience postnatal depression and a lack of social support, affecting their life satisfaction. However, there is a lack of studies investigating the application of guided antenatal education support programs to deal with such issues. Purpose: The study aimed to evaluate the effects of guided antenatal education support programs on postnatal depression, social support, and life satisfaction among first-time mothers. Methods: This quasi-experimental study involved a total of 72 first-time mothers. Convenience sampling was applied for participant selection, and no randomization was used. The participants were equally divided into the intervention group and the control group. A self-administrated questionnaire was used for data collection during the antenatal period (pretest) and six weeks postpartum (posttest). The risk of postnatal depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS). In addition, the Multidimensional Scale of Perceived Social Support (MSPSS) and the Satisfaction with Life Scale (SWLS) were used to assess social support, and life satisfaction, respectively. The intervention group received a guided antenatal education support program, consisting of antenatal education sessions plus an extra 15-minute discussion and a support guidebook. The data were analyzed using a paired t-test and an independent t-test. Results: There was a significant reduction in the risk of postnatal depression score in the intervention group (p

Introduction: SABINA III assessed short-acting β2-agonist (SABA) prescription patterns and their association with asthma-related outcomes globally. Herein, we examined SABA prescription and clinical outcomes in the Malaysian cohort of SABINA III. Methods: In this observational, cross-sectional study, patients (≥12 years) were recruited between July and December 2019 from 15 primary and specialty care centres in Malaysia. Prescribed asthma treatments and severe exacerbation history within 12 months prior and asthma symptom control during the study visit were evaluated. Associations of SABA prescription with asthma control and severe exacerbation were analysed using multivariable regression models. Results: Seven hundred thirty-one patients (primary care, n=265 [36.3%]; specialty care, n=466 [63.7%]) were evaluated. The prevalence of SABA over-prescription (≥3 SABA prescriptions/year) was 47.4% (primary care, 47.1%; specialty care, 47.6%), 51.8% and 44.5% among all patients and patients with mild and moderate-to-severe asthma, respectively. Altogether 9.0% (n=66) purchased SABA without a prescription; among them, 43.9% (n=29) purchased ≥3 inhalers. The mean (standard deviation) number of severe asthma exacerbations was 1.38 (2.76), and 19.7% (n=144) and 25.7% (n=188) had uncontrolled and partly controlled symptoms, respectively. Prescriptions of ≥3 SABA inhalers (vs 1–2) were associated with lower odds of at least partly controlled asthma (odds ratio=0.42; 95% confidence interval [CI]=0.27–0.67) and higher odds of having severe exacerbation(s) (odds ratio=2.04; 95% CI=1.44–2.89). Conclusion: The prevalence of SABA over-prescription in Malaysia is high, regardless of the prescriber type, emphasising the need for healthcare providers and policymakers to adopt latest evidence-based recommendations to address this public health concern.

Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver diseases, arise from non-alcoholic fatty liver (NAFL) characterized by excessive fat accumulation as triglycerides. Although NAFL is benign, it could progress to non-alcoholic steatohepatitis (NASH) manifested with inflammation, hepatocyte damage and fibrosis. A subset of NASH patients develops end-stage liver diseases such as cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD is highly complex and strongly associated with perturbations in lipid and glucose metabolism. Lipid disposal pathways, in particular, impairment in condensation of acetyl-CoA derived from β-oxidation into ketogenic pathway strongly influence the hepatic lipid loads and glucose metabolism. Current evidence suggests that ketogenesis dispose up to two-thirds of the lipids entering the liver, and its dysregulation significantly contribute to the NAFLD pathogenesis. Moreover, ketone body administration in mice and humans shows a significant improvement in NAFLD. This review focuses on hepatic ketogenesis and its role in NAFLD pathogenesis. We review the possible mechanisms through which impaired hepatic ketogenesis may promote NAFLD progression. Finally, the review sheds light on the therapeutic implications of a ketogenic diet in NAFLD.

Simple Summary: At least 50% of breast cancers are estimated to belong to the 'human epidermal growth factor receptor 2 (HER2)-low' category. Since HER2-low breast cancer is amenable to targeted treatment with anti-HER2 antibody-drug conjugates, accurate assessment of patients' HER2-low status is crucial for qualifying them for this treatment. Despite the 2018 American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) guidelines recognizing the clinical relevance of HER2-low testing, discrepancies in HER2 testing across laboratories globally hinder an accurate identification of HER2-low patients. To overcome these limitations, this consensus guideline aims to elucidate best practices for HER2 testing and HER2-low scoring in breast cancer. This guideline, while adapted to the Malaysian landscape, reflects recommendations from the latest international guidelines to guide pathologists in performing HER2 testing and address common issues faced in the Malaysian context, thus improving the quality of HER2 testing and ensuring the best available cancer care. Breast cancer is one of the most common cancers in Malaysia. Recently, a new nomenclature was introduced for breast cancers with human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 1+, or 2+ with negative in situ hybridization (ISH), i.e., HER2-low breast cancer. In current clinical practice, these breast cancers are reported as HER2-negative. Clinical trials have shown that HER2-low breast cancer benefits from targeted therapy with anti-HER2 antibody-drug conjugates. Unfortunately, various challenges and obstacles are faced by local pathologists in HER2 testing, which may jeopardize the standard of care for patients with HER2-low breast cancer. This consensus guideline aims to elucidate standard practices pertaining to HER2 testing and HER2-low interpretation in Malaysia. Topics discussed among a panel of local experts include tissue sampling and handling, assay and antibody selection, result interpretation and reporting, and quality assurance. Practice recommendations made in this consensus guideline reflect current international guidelines and, where appropriate, adapted to the Malaysian landscape. [ABSTRACT FROM AUTHOR]

Background: Thermogenic beige adipocytes, which dissipate energy as heat, are found in neonates and adults. Recent studies show that neonatal beige adipocytes are highly plastic and contribute to >50% of beige adipocytes in adults. Neonatal beige adipocytes are distinct from recruited beige adipocytes in that they develop independently of temperature and sympathetic innervation through poorly defined mechanisms. Methods: We characterized the neonatal beige adipocytes in the inguinal white adipose tissue (iWAT) of C57BL6 postnatal day 3 and 20 mice (P3 and P20) by imaging, genome-wide RNA-seq analysis, ChIP-seq analysis, qRT-PCR validation, and biochemical assays. Results: We found an increase in acetylated histone 3 lysine 27 (H3K27ac) on the promoter and enhancer regions of beige-specific gene UCP1 in iWAT of P20 mice. Furthermore, H3K27ac ChIP-seq analysis in the iWAT of P3 and P20 mice revealed strong H3K27ac signals at beige adipocyte-associated genes in the iWAT of P20 mice. The integration of H3K27ac ChIP-seq and RNA-seq analysis in the iWAT of P20 mice reveal epigenetically active signatures of beige adipocytes, including oxidative phosphorylation and mitochondrial metabolism. We identify the enrichment of GA-binding protein alpha (GABPα) binding regions in the epigenetically active chromatin regions of the P20 iWAT, particularly on beige genes, and demonstrate that GABPα is required for beige adipocyte differentiation. Moreover, transcriptomic analysis and glucose oxidation assays revealed increased glycolytic activity in the neonatal iWAT from P20. Conclusions: Our findings demonstrate that epigenetic mechanisms regulate the development of peri-weaning beige adipocytes via GABPα. Further studies to better understand the upstream mechanisms that regulate epigenetic activation of GABPα and characterization of the metabolic identity of neonatal beige adipocytes will help us harness their therapeutic potential in metabolic diseases. [ABSTRACT FROM AUTHOR]

Background & Aims: Fatty liver or nonalcoholic fatty liver disease (NAFLD) is the most common liver disease associated with comorbidities such as insulin resistance and cardiovascular and metabolic diseases. Chronic activation of hypoxic signaling, in particular, hypoxia-inducible factor (HIF)2α, promotes NAFLD progression by repressing genes involved in fatty acid β-oxidation through unclear mechanisms. Therefore, we assessed the precise mechanism by which HIF2α promotes fatty liver and its physiological relevance in metabolic homeostasis. Methods: Primary hepatocytes from VHL (VhlΔHep) and PPARα (Ppara-null) knockout mice that were loaded with fatty acids, murine dietary protocols to induce hepatic steatosis, and fasting-refeeding dietary regimen approaches were used to test our hypothesis. Results: Inhibiting autophagy using chloroquine did not decrease lipid contents in VhlΔHep primary hepatocytes. Inhibition of ERK using MEK inhibitor decreased lipid contents in primary hepatocytes from a genetic model of constitutive HIF activation and primary hepatocytes loaded with free fatty acids. Moreover, MEK-ERK inhibition potentiated ligand-dependent activation of PPARα. We also show that MEK-ERK inhibition improved diet-induced hepatic steatosis, which is associated with the induction of PPARα target genes. During fasting, fatty acid β-oxidation is induced by PPARα, and refeeding inhibits β-oxidation. Our data show that ERK is involved in the post-prandial repression of hepatic PPARα signaling. Conclusions: Overall, our results demonstrate that ERK activated by hypoxia signaling plays a crucial role in fatty acid β-oxidation genes by repressing hepatocyte PPARα signaling.

Introduction: Polycystic Ovarian Syndrome (PCOS) is a common endocrine disorder encountered in female. Multimodular interventions of lifestyle modifications emphasise bearable weight loss through dietary, exercise, and behavioural modification. The timely recognition, understanding, and handling of clinical characteristics of this syndrome shall prevent long-term health issues. Aim: To evaluate the efficacy of multimodular interventions on symptoms of PCOS and the quality of life of women with PCOS. Materials and Methods: A pilot study was conducted at Father Muller College of Nursing, Mangaluru, Karnataka, India, between May 2019 to February 2020. The female diagnosed with PCOS were selected through a purposive sampling technique, from two tertiary settings (15 subjects for the intervention group and 15 for the control group). The multimodular interventions (diet, exercises, and behavioural modifications) were provided to the study group. Follow-up was done in the 2nd, 4th and 6th month. The control group subjects continued the regular medical treatment and followed-up at 6th month. The intervention and control group results were compared in the 6th month. The tools used for data collection were baseline variables, PCOS symptom assessment tool, and World Health Organisation Quality of Life questionnaire (WHOQOL-BREF) tool. Results: The mean age of study participants was 24.26±3.84 years in the intervention, and 24.20±3.54 years in the control group. A significant improvement in the waist-hip ratio, hirsutism acne (p-value

Performance, cost, and aesthetics are all difficult to beat in today’s expanding distributed rooftop solar sector, and flat-plate PV is no exception. Photovoltaics will be able to take advantage of some of their most significant advantages as a result of this marketplace, including the elimination of transmission losses and the generation of power at the point of sale. Concentrated photovoltaic (CPV) technology, on the other hand, represents a viable alternative in the quest for ever-lower normalised energy costs and ever-shorter energy payback times. Material, components, and manufacturing techniques from allied sectors, particularly the power electronics industry, have been adapted to lower system costs and time-to-market for the system under development. The LFR is less than 30 mm wide to maximise thermal efficiency, and a densely packed cell array has been used to maximise electrical output. The Matlab simulations show that the proposed machine learning-based LFR technique has a greater concentration rate than the present LFR method, as demonstrated by the results.

The choice of the optimal orientation of the solar panels is by far one of the most important issues in the practical application of solar installations. The use of phase changing materials (PCMs) is an efficient approach of storing solar thermal energy. Because PCMs are isothermal in nature, they provide better density energy storage and the capacity to function across a wide temperature range. Unfortunately, this feature is very rare on various solar power panels; however, ignoring it can reduce the performance of the panels to unacceptable levels. The fact is that the angle of incidence of rays on the surface greatly affects the reflection coefficient and, consequently, the role of unacceptable solar energy. In this paper, a smart energy harvesting model was proposed. In the case of glass, when the angle of incidence varies vertically from its surface to 30, the reflection coefficient is practically unchanged and slightly less than 5%, i.e., more than 95% of the radiation goes inwards. Furthermore, the reflection increase is noticeable, and the area of the reflected radiation by 60 doubles to almost 10%. At an angle of incidence of 70, it reflects 20% of the radiation, and at 80, 40%. For most other objects, the dependence of the reflection magnitude on the angle of incidence is approximately the same.

In the present work, brownmillerite KBiFe2O5 (KBFO), a relatively new multifunctional compound, has been explored as an electrode material for applications in supercapacitors. Polycrystalline KBFO is synthesized via citrate combustion method. The phase formation, crystallinity, composition and morphology of KBFO samples are investigated using XRD, HRTEM, XPS and FESEM. As synthesized KBFO sample possesses rectangular rod-like morphology with monoclinic crystal system. The electrochemical properties of KBFO were analyzed using Galvanostatic charge/discharge (GCD), Cyclic voltammetry (CV) and Electrochemical Impedance Spectroscopy (EIS) in acidic, alkaline and neutral electrolyte media. GCD results show a promising energy storage property with remarkable 100% capacitive retention after 1000 cycles. CV results also establish the pseudocapacitive nature of KBFO in all electrolyte media. These features support the feasibility of exploitation of KBFO for advanced energy storage applications.

Mitochondria play important roles in regulating cell bioenergetics status and reactive oxygen species (ROS) generation. ROS-induced mitochondrial damage is among the main intracellular signal inducers of autophagy. Autophagy is a cellular catabolic process that regulates protein and organelle turnover, while a selective form of autophagy, mitophagy, specifically targets dysfunctional mitochondrial degradation. This study aims to measure the levels of autophagy, mitophagy, oxidative stress, and apoptosis in invasive breast carcinoma tissues using immunohistochemistry (IHC). Tissue microarrays of 76 patients with breast cancer were stained with six IHC markers (MnSOD, Beclin-1, LC3, BNIP3, Parkin, and cleaved caspase 3). The expression intensity was determined for each tumor tissue and the adjacent tumor-matched control tissues. Intermediate and strong staining scores of MnSOD, Beclin-1, LC-3, BNIP-3, and Parkin were significantly higher in tumor tissues compared to the adjacent matched control. The scoring intensity was further classified into tissues with negative staining and positive staining, which showed that positive scores of Beclin-1 and Parkin were significantly high in tumor tissues compared to other markers. Positive association was also noted between BNIP-3 and Beclin-1 as well as LC-3 and cleaved caspase-3 immunostaining. To our knowledge, this is one of the first studies that measure both mitophagy and autophagy in the same breast cancer tissues and the adjacent matched control. The findings from this study will be of great potential in identifying new cancer biomarkers and inspire significant interest in applying anti-autophagy therapies as a possible treatment for breast cancer.

Pneumopericardium is defined as the presence of gas in pericardial space. In adults, it may be seen in the context with severe blunt or penetrating chest trauma. The incidence of pneumopericardium is 0.8% and nearly 60% of the cases are due to trauma. A 55-year-old female admitted with the complaints of cough, breathlessness, left-sided chest pain – a case of left secondary spontaneous pneumothorax with the Intercostal drainage tube (ICD) in situ, her computed tomography image revealed pneumopericardium, residual left pneumothorax with ICD tube in the subcutaneous plane. After successful repositioning of ICD tube, pneumopericardium and left pneumothorax both got resolved. Her sputum examination results were positive for Mycobacterium tuberculosis, and she started on Anti-tubercular treatment (ATT). Her condition was gradually improved; the ICD tube was removed and discharged from the hospital in stable condition. On follow-up, both clinical and radiological improvement was there. A severe bout of cough (Macklin effect) and fistulous communication could be the two possible mechanisms for spontaneous pneumopericardium. Treatment of the underlying condition will resolve the pneumopericardium.

Nutritional intervention is a key strategy in the control and management of non-communicable diseases. Here, initially, we evaluated the effects of carrot juice (CJ) on some of the physical and biochemical parameters in rats fed with high-fructose diet, then in type 2 diabetic subjects. For the animal study, weanling male Wistar rats were given control (n = 6) or high fructose (HFr; n = 24) diet for 8 weeks. Then, the HFr group rats were subdivided into 4 groups (n = 6 in each) and continued either on HFr diet or shifted to control diet, with or without CJ (0.3 mg β-carotene) ingestion orally for 8 weeks. At the end, the ingestion of CJ reversed the HFr-induced adiposity (23 ± 1.6 vs 18 ± 1.1, P = .038), hypertriglyceridemia (182 ± 18.2 vs 90 ± 10.5 mg/dL, P

Introduction: Diabetes Mellitus is a common medical problem that is very often seen in pregnancy in the present era. Pregnant women should keep in mind their health and lifestyle considerations or else pregnancy will end up with many complications. Pre-existing factors and pregnancy factors will be contributing and make pregnancy more complicated. Exercises are recommended as a healthy practice which prevents many diseases and provides a healthy life. Aim: To evaluate the glycaemic level by focusing on exercises to improve the maternal outcome. Materials and Methods: A Pilot study with Quasi-experimental pre-post control group design with 30 Gestational Diabetes Mellitus (GDM) women (15 in each group) were selected who met the inclusion and exclusion criteria. The study was conducted in tertiary care Hospital between June 2019 and December 2019. Based on the convenience sampling technique, the setting was selected and a simple random technique was adopted to select the subjects. The 15 subjects were included in each groups, both intervention and control group. Exercises were taught for the interventional group of women for 12 weeks. Regular treatment was continued for both groups which include medication, diet and regular walking. Pre-test and post-test glycaemic scores were done for both the groups. Mann-whitney test, ANOVA, post-hoc test, paired Eta square were also used and IBM Statistical Package for the Social Sciences (SPSS) version 23.0 was used. Results: The study shows there was a significant difference in the pre-Fasting Blood Sugar (FBS) and post FBS values in the intervention group p-value 0.05. Conclusion: Regular moderate-intensity aerobic and resistance exercise training during pregnancy is associated with lower blood glucose level. Thus, study concluded that exercise has a moderate effect on glycaemic control.

Background & Aims: Thrombospondin 1 (TSP1) is a multifunctional matricellular protein. We previously showed that TSP1 has an important role in obesity-associated metabolic complications, including inflammation, insulin resistance, cardiovascular, and renal disease. However, its contribution to obesity-associated non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD or NASH) remains largely unknown; thus, we aimed to determine its role. Methods: High-fat diet or AMLN (amylin liver NASH) diet-induced obese and insulin-resistant NAFLD/NASH mouse models were utilised, in addition to tissue-specific Tsp1-knockout mice, to determine the contribution of different cellular sources of obesity-induced TSP1 to NAFLD/NASH development. Results: Liver TSP1 levels were increased in experimental obese and insulin-resistant NAFLD/NASH mouse models as well as in obese patients with NASH. Moreover, TSP1 deletion in adipocytes did not protect mice from diet-induced NAFLD/NASH. However, myeloid/macrophage-specific TSP1 deletion protected mice against obesity-associated liver injury, accompanied by reduced liver inflammation and fibrosis. Importantly, this protection was independent of the levels of obesity and hepatic steatosis. Mechanistically, through an autocrine effect, macrophage-derived TSP1 suppressed Smpdl3b expression in liver, which amplified liver proinflammatory signalling (Toll-like receptor 4 signal pathway) and promoted NAFLD progression. Conclusions: Macrophage-derived TSP1 is a significant contributor to obesity-associated NAFLD/NASH development and progression and could serve as a therapeutic target for this disease. Lay summary: Obesity-associated non-alcoholic fatty liver disease is a most common chronic liver disease in the Western world and can progress to liver cirrhosis and cancer. No treatment is currently available for this disease. The present study reveals an important factor (macrophage-derived TSP1) that drives macrophage activation and non-alcoholic fatty liver disease development and progression and that could serve as a therapeutic target for non-alcoholic fatty liver disease/steatohepatitis.

Interleukin-10 (IL-10) is a critical cytokine used by immune cells to suppress inflammation. Paradoxically, immune cell–derived IL-10 can drive insulin resistance in obesity by suppressing adipocyte energy expenditure and thermogenesis. However, the source of IL-10 necessary for the suppression of adipocyte thermogenesis is unknown. We show here that CD4+Foxp3+ regulatory T cells (Tregs) are a substantial source of IL-10 and that Treg-derived IL-10 can suppress adipocyte beiging. Unexpectedly, Treg-specific loss of IL-10 resulted in increased insulin sensitivity and reduced obesity in high-fat diet–fed male mice. Mechanistically, we determined that Treg-specific loss of the transcription factor Blimp-1, a driver of IL-10 expression by Tregs, phenocopied the Treg-specific IL-10–deficient mice. Loss of Blimp-1 expression in Tregs resulted in reduced ST2+KLRG1+, IL-10-secreting Tregs, particularly in the white adipose tissue. Blimp-1–deficient mice were protected from glucose intolerance, insulin resistance, and diet-induced obesity, through increased white adipose tissue browning. Taken together, our data show that Blimp-1–regulated IL-10 secretion by Tregs represses white adipose tissue beiging to maintain adipose tissue homeostasis.

The role of sexual dimorphic adipose tissue fat accumulation in the development of insulin resistance is well known. However, whether vitamin A status and/or its metabolic pathway display any sex- or depot (visceral/subcutaneous)-specific pattern and have a role in sexual dimorphic adipose tissue development and insulin resistance are not completely understood. Therefore, to assess this, 5 weeks old Wistar male and female rats of eight from each sex were provided either control or diabetogenic (high fat, high sucrose) diet for 26 weeks. At the end, consumption of diabetogenic diet increased the visceral fat depots (p

The two-fluid Eulerian model, coupled with the heat flux partitioning model, is being widely used to predict subcooled flow boiling characteristics and critical heat flux (CHF). The heat flux partitioning model relies on essential parameters like bubble departure diameter, departure frequency, and nucleation site density. Mainly, performing experiments to determine bubble departure diameters and frequencies is challenging. Another approach is to use semi-mechanistic models; however, even such models rely on some crucial parameters like advancing contact angle, receding contact angle, contact diameter, and many others. In this study, the influence of such parameters, and the role of different forces in determining bubble departure diameters and departure frequencies, at high-pressure conditions is studied. Moreover, a parametric analysis is carried to understand the influence of such parameters on CHF prediction.

In subcooled boiling flows beyond a certain heat flux, heat transfer is hampered due to a phenomenon known as Departure from Nucleate Boiling (DNB). Conducting DNB experiments at one-to-one nuclear reactor operating conditions is highly challenging and expensive. Another alternative approach is to use Look-up table data. However, its applicability is limited due to its dependence on rod bundle correction factors. In the present investigation, a state-of-the-art Eulerian-Eulerian two-fluid model coupled with an extended heat flux partitioning model is used to predict DNB in tubes and rod bundles with square and hexagonal lattices (relevant to Pressurized Water Reactors). In this approach, bubble departure characteristics are modeled using semi-mechanistic models based on force balance analysis. The predicted DNB values are compared with experimental and Look-up table data and found out to be within 1.8% to 20%.

Abstract Background Graphite carbon nanofibers (GCNF) have emerged as a potential alternative of carbon nanotubes (CNT) for various biomedical applications due to their superior physico-chemical properties. Therefore in-depth understanding of the GCNF induced toxic effects and underlying mechanisms in biological systems is of great interest. Currently, autophagy activation by nanomaterials is recognized as an emerging toxicity mechanism. However, the association of GCNF induced toxicity with this form of cell death is largely unknown. In this study, we have assessed the possible mechanism; especially the role of autophagy, underlying the GCNF induced toxicity. Methods Human lung adenocarcinoma (A549) cells were exposed to a range of GCNF concentrations and various cellular parameters were analyzed (up to 48 h). Transmission electron microscopy, immunofluorescent staining, western blot and quantitative real time PCR were performed to detect apoptosis, autophagy induction, lysosomal destabilization and cytoskeleton disruption in GCNF exposed cells. DCFDA assay was used to evaluate the reactive oxygen species (ROS) production. Experiments with N-acetyl-L-cysteine (NAC), 3-methyladenine (3-MA) and LC3 siRNA was carried out to confirm the involvement of oxidative stress and autophagy in GCNF induced cell death. Comet assay and micronucleus (MN) assay was performed to assess the genotoxicity potential. Results In the present study, GCNF was found to induce nanotoxicity in human lung cells through autophagosomes accumulation followed by apoptosis via intracellular ROS generation. Mechanistically, impaired lysosomal function and cytoskeleton disruption mediated autophagic flux blockade was found to be the major cause of accumulation rather than autophagy induction which further activates apoptosis. The whole process was in line with the increased ROS level and their pharmacological inhibition leads to mitigation of GCNF induced cell death. Moreover the inhibition of autophagy attenuates apoptosis indicating the role of autophagy as cell death process. GCNF was also found to induce genomic instability. Conclusion Our present study demonstrates that GCNF perturbs various interrelated signaling pathway and unveils the potential nanotoxicity mechanism of GCNF through targeting ROS-autophagy-apoptosis axis. The current study is significant to evaluate the safety and risk assessment of fibrous carbon nanomaterials prior to their potential use and suggests caution on their utilization for biomedical research.